There are a variety of situations in which it is advantageous to have a system for delivering biologically active substances in bursts or pulses at predetermined times without human or mechanical intervention.
For example, some hormones only exhibit their effect if they are administered in pulses. At the present time, patients and laboratory animals, in order to be administered periodic pulses of hormones, wear hormone pumps that are programmed to inject hormones at particular intervals. These pump-like devices are subject to leaks, require maintenance, and are cumbersome. By reason of their size, they are unsuitable for rats, mice and other small laboratory animals.
A small implantable, biocompatible and biodegradable system which would make the controlled administration of bioactive agents to both animals and man, easier, less painful, and less time consuming, and which additionally is less cumbersome than the portable pumps, is therefore desirable.
For example, in a classical immunization procedure, which may achieve short-term immunity, a single dose of antigen is delivered in one injection. Antigen initially is present at a high level for a short time, but is soon lost from the inoculation site. However, with repeated treatments, a strengthened immune response is evoked which may impart lasting immunity. An implantable, biocompatible and biodegradable polymeric system for immunization offers several attractive features. Such a controlled release system would deliver a second burst of antigen at a predetermined amount of time following a first burst. The second burst would elicit a secondary immune response without the need for a second or third booster vaccination.
Another example in which a controlled pulsed release of a bioactive substance would be desirable is in the distribution of pesticides on, for example farm land. In some cases, it is desirable to release some insecticides or insect pheromones in response to rain. This is desirable because many insect pests hatch shortly after rain, when fields are too wet for farmers to enter with tractors to spread pesticides. Thus, rather than apply unnecessary pesticides continuously, thereby possibly killing helpful insects and spiders, a biodegradable bursting pesticide delivery system could be spread at some time before a rain storm and used to deliver the insecticide only when needed. The individual bursting units of this system, which would release pesticides at a predetermined time after rain or exposure to water, would be much more efficient and less damaging to the environment.
Previously, long acting polymeric release devices have been developed which provide near zero order or continuous release of an active agent. The continuous or uniform release of an active agent is not ideal in many instances, such as those discussed above.
U.S. Pat. No. 4,591,496 issued to Baker, discloses a osmotic bursting dispenser having an active agent incorporated in an enclosed semipermeable container. Although several parameters which affect bursting time are discussed, no empirical or theoretical relationships are disclosed. In addition, although the dispenser is suggested for use as an implant in animals, the container materials suggested are non-biodegradable.